Major objectives of this program are to study the natural history of group B streptococcal (GBS) and pneumococcal infections. To accomplish these goals, a team of 7 principal investigators, 13 co-investigators and 2 collaborators has been organized from the disciplines of pediatrics, obstetrics, medicine and microbiology. Proportionately more effort is devoted to GBS studies, which include extensive epidemiological investigations in pregnant women, parturients, newborns, and young infants. GBS carriage and disease rates in an urban and suburban population will be compared and clinical, bacterial and immunological factors predispoding to infection defined. Early and late forms of GBS disease in infants are studied. The role of GBS in pathogenesis of respiratory distress and pneumonia in newborns and urinary tract infection in pregnant women will also be prospectively studied. Plans are being developed for a study of maternal prophylaxis to prevent early onset GBS disease. Immunological studies, using purified GBS antigens, will determine the class of antibody and the respective roles of humoral and mucosal antibody in host defense against GBS. Methods include ELISA, neutrophil iodination and RIA. Biochemical characteristics of GBS antigen will be further characterized. A murine model will be developed to study mucosal immunity to GBS and to evaluate potential for an orally administered vaccine. A separate animal model, using newborn lambs, will be used to investigate mechanisms of cardiopulmonary dysfunction induced by GBS. Studies of pneumococcal infection and immunity will focus on specific diseases: pneumonia, sepsis, meningitis and othitis media. Basic and clinical investigations of specific and nonspecific host defense mechanisms will be pursued. The latter includes CRP and antibody to phosphocholine. Similar immunologic methods are used in GBS and pneumococcal investigations. Alterations in platelet function and release of specific mediators that contribute to shock will also be studies in seriously ill infants. We will continue to develop contemporary epidemiological data on pneumococcal disease in children and adults, including high-risk vaccinated subjects.